期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 167, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejps.2021.105992
关键词
Triple negative breast cancer; Paclitaxel; Niclosamide; Nanocrystal; Thermosensitive hydrogel; Intratumoral drug delivery
资金
- National Natural Science Foundation of China [81673830]
- six talent peaks project of Jiangsu Province [YY053]
- Major Project and Double first-class innovative team [CPU2018GY28]
- National Science and Technology Major Project [2017zx09101001005]
An injectable PTX and NLM nanocrystals co-loaded PLGA-PEG-PLGA thermosensitive hydrogel was designed for intratumoral treatment of TNBC. The formulation realized high drug loading and appropriate particle size, displaying sustained drug release and high tumor growth inhibition rate in vivo, with potential to prevent TNBC recurrence and metastasis.
Triple negative breast cancer (TNBC) is the most dangerous subtype of breast cancer accompanying by unfavorable prognosis due to lack of specific therapeutic targets. Paclitaxel (PTX) is the first-line chemotherapeutic drug for TNBC and niclosamide (NLM) was identified as an inhibitor for TNBC and breast cancer stem cells (BCSCs). Intratumoral drug delivery system was a hopeful alternative for chemotherapeutic drug administration due to its targeting efficiency with lower systemic toxicity. Herein, an injectable PTX nanocrystals (PTX-NCs) and NLM nanocrystals (NLM-NCs) co-loaded PLGA-PEG-PLGA thermosensitive hydrogel (PN-NCs-Ts Gel) was designed for TNBC intratumoral treatment. The final formulation realized high drug loading and appropriate particle size. PN-NCs-Ts Gel displayed sustained drug release for up to 8 days in vitro. In vitro antitumor tests observed synergetic effects of combined therapy in terms of inhibiting cell proliferation and migration, inducing apoptosis. In vivo combined therapy presented a tumor growth inhibition rate about 68.8% and desired safety. Moreover, tumors after PN-NCs-Ts Gel intratumoral injection possessed the lowest ratio of BCSCs, exhibiting this formulation had good ability in suppressing BCSCs and therefore could possibly prevent TNBC recurrence and metastasis. These results suggested that PN-NCs-Ts Gel could be a promising strategy for TNBC treatment.
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